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The objective of this study was to evaluate incidence and risk factors of postoperative infections, with emphasis on antibiotic prophylaxis, in a series of 4578 craniotomies. A prospective database was implemented for surveillance of postcraniotomy infections. During period A, no antibiotic prophylaxis was prescribed for scheduled, clean craniotomies, lasting less than 4 h, whereas emergency, clean-contaminated or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. During period B, prophylaxis was given to every craniotomy. The effect of prophylaxis on craniotomy infections, independently of other risk factors, was studied by multivariate analysis. The overall infection rate was 6.6%. CSF leak, male gender, surgical diagnosis, surgeon, early re-operation, surgical duration and absence of prophylaxis were independent risk factors. CSF leak had the highest odds ratio. Antibiotic prophylaxis …